The purpose of this project is to analyze, at the gene level, a collection of germinal mutations produced by various chemicals in the course of experiments using biochemical specific locus test and other mutation assay systems. The genes to be analyzed encode HBA and HBB. Multiple independently induced and/or spontaneous variants for each of these genes are analyzed by DNA probes produced from the normal (wild-type) mRNA or DNA for aberrant gene structure, processing, and expression. Analysis of a naturally occurring Beta-globin deficiency has recently been completed and the mutation shown to be a small deletion affecting only the Beta-globin gene. The mutation is designated Hbb(th-1) for Beta-thalassemia and represents the only non-human Beta-thalassemia yet discovered. Biochemical analysis of an induced Alpha-globin mutation, done in collaboration with Dr. R. Popp, Oak Ridge National Laboratory, revealed an amino acid substitution at Alpha89His Leu, likely produced by a transversion type of base substitution.